The objective of this research is to analyze normal and abnormal mechanisms of development through use of mutant genes of the mouse. The mutations to be studies include: (1) congenital hydrocephalus (ch), a recessive mutation causing severe early embryonic hydrocephalus, widespread skeletal defects, and excess mesonephric tubules leading to urogenital abnormalities; (2) tight skin (Tsk), a dominant mutation causing extensive hyperplasia of the loose connective tissue, enlarged heart and lungs, and abnormally long cartilages and long bones; and (3) a recessive mutation causing runting and early death associated with an abnormally slow rate of respiration. Other mutations will be studied as time permits. The methods used will be mostly morphological, but will include tissue culture and physiological studies where appropriate.